Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Altered hemispheric lateralization of cortico-basal ganglia-thalamic network associated with gene expression and neurotransmitter profiles as potential biomarkers for panic disorder","authors":"Yiding Han ,&nbsp;Haohao Yan ,&nbsp;Xiaoxiao Shan ,&nbsp;Huabing Li ,&nbsp;Feng Liu ,&nbsp;Ping Li ,&nbsp;Yonggui Yuan ,&nbsp;Dongsheng Lv ,&nbsp;Wenbin Guo","doi":"10.1016/j.pnpbp.2025.111441","DOIUrl":"10.1016/j.pnpbp.2025.111441","url":null,"abstract":"<div><div>Functional brain lateralization, a key feature of the human brain that shows alterations in various mental disorders, remains poorly understood in panic disorder (PD), and its investigation may provide valuable insights into the neurobiological underpinnings of psychiatric conditions. This study investigates hemispheric lateralization in drug-naive patients with PD before and after treatment, explores its associations with gene expression and neurotransmitter profiles, and examines its utility for diagnosis and treatment outcome prediction. Fifty-eight patients and 85 healthy controls (HCs) were enrolled. Clinical assessments and resting-state functional magnetic resonance imaging scans were conducted before and after a 4-week paroxetine monotherapy. Intra-hemispheric functional connectivity strength (FCS), inter-hemispheric FCS, and parameter of asymmetry (PAS) were calculated. Imaging-transcriptomic and imaging-neurotransmitter correlation analyses were conducted. PAS was used in machine learning models for classification and treatment outcome prediction. Compared with HCs, patients exhibited enhanced intra-hemispheric FCS and decreased PAS in the caudate nucleus/pallidum and thalamus, with associated genes, dopamine and serotonin receptor densities, and vesicular acetylcholine transporter densities linking these lateralization alterations to neural signaling and synaptic function. FCS and PAS results were consistent across different correlation thresholds (0.15, 0.2, and 0.25). No significant changes in FCS or PAS were observed following treatment. PAS demonstrated excellent performance in classification (accuracy = 75.52 %) and treatment outcomes prediction (<em>r</em> = 0.763). Hemispheric lateralization in the cortico-basal ganglia-thalamic network was significantly altered in patients with PD, with these changes linked to disruptions in genes and neurotransmitter profiles which are associated with neural signal transduction and synaptic function. PAS shows promise as a biomarker for PD diagnosis and treatment outcome prediction.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111441"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BDNF as a potential predictor of cardiac and depressive outcomes in patients 6- months after PCI with stent placement","authors":"Sara Medved ,&nbsp;Alma Mihaljević-Peleš ,&nbsp;Joško Bulum ,&nbsp;Slavica Sović ,&nbsp;Lana Ganoci ,&nbsp;Nada Božina ,&nbsp;Maja Bajs Janović ,&nbsp;Marina Šagud ,&nbsp;Ivan Jurak","doi":"10.1016/j.pnpbp.2025.111442","DOIUrl":"10.1016/j.pnpbp.2025.111442","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is one of the most common cardiovascular diseases, often requiring percutaneous coronary intervention (PCI). Depressive symptoms can significantly impair post-PCI recovery. Brain-derived neurotrophic factor (BDNF) has been implicated as a contributor to CAD and depression, however, its exact role remains unclear. Therefore, the aim of this study is to evaluate the association between serum BDNF levels and cardiac and depression outcomes following PCI with stent placement.</div><div>This cohort study, with a 6-month follow-up, collected socio-economic, depression and cardiac data, along with serum samples for BDNF level evaluation. Depression was assessed using the Hamilton Rating Scale for Depression (HAM<img>D) scale and Patient Health Questionnaire-15 (PHQ-15). Cardiac assessment included the Seattle Angina Questionnaire Short Form (SAQ-7) and Duke Activity Status Index (DASI). The final sample included 76 participants (mean age 61.4 years, 81.6 % male), of whom 41 presented with depression symptoms. Serum BDNF levels did not differ between groups but were positively correlated with DASI score at baseline and DASI, Physical Limitation SAQ-7 domain, and PHQ-15 scores in the follow-up. Hierarchical regression models showed that serum BDNF level was a significant positive predictor of DASI scores at follow-up (adjusted R² = 0.298), but not of other variables.</div><div>Our findings indicate that higher BDNF levels correlate with improved cardiac outcomes post-PCI with stent placement, independent of baseline cardiac status or depression. That suggests that serum BDNF levels may serve as a biomarker for post-PCI recovery, likely due to its role in cardiac myocyte function and vascular stability.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111442"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Exploring the relationship between socioeconomic deprivation index and Alzheimer's disease using summary-level data: from genetic correlation to causality” [Progress in Neuropsychopharmacology & Biological Psychiatry 123 (2023) 110700]","authors":"Jing Dai ,&nbsp;Yue Xu ,&nbsp;Ting Wang ,&nbsp;Ping Zeng","doi":"10.1016/j.pnpbp.2025.111420","DOIUrl":"10.1016/j.pnpbp.2025.111420","url":null,"abstract":"","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111420"},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of the number of psychiatric hospitalizations and diagnosis in serum levels of CCL11 and GDF15 in individuals with stable schizophrenia, bipolar disorder, and major depressive disorder: The compass between neuro and somatoprogression","authors":"Monise Costanzi ,&nbsp;Jeferson F. Goularte ,&nbsp;Luis Henrique Toledo da Silva ,&nbsp;Marina Siebert ,&nbsp;Isabela Drehmer Merenda de Carvalho ,&nbsp;Paola Rampelotto Ziani ,&nbsp;Iohanna Deckmann ,&nbsp;Júlio Santos-Terra ,&nbsp;Carmem Gottfried ,&nbsp;Marcelo P. Fleck ,&nbsp;Marco Antonio Caldieraro ,&nbsp;Adriane R. Rosa ,&nbsp;Clarissa S. Gama","doi":"10.1016/j.pnpbp.2025.111446","DOIUrl":"10.1016/j.pnpbp.2025.111446","url":null,"abstract":"<div><div>Severe psychiatric disorders significantly impact quality of life and life expectancy, contributing to increased years lived with disability. Most deaths in these individuals result from chronic clinical conditions such as cardiovascular diseases. There is evidence that immune-inflammatory activation, increased oxidative stress and abnormalities in mitochondrial function play a role in the pathophysiology of major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). These inflammatory-oxidative processes worsen with each mood and/or psychotic episode. This study aimed to investigate serum levels of the pro-inflammatory chemokine CCL11 and the stress response cytokine GDF15 in individuals with SCZ, BD, and MDD compared to healthy controls (HC). A total of 558 participants (147 with SCZ, 130 with BD, 157 with MDD, and 114 HC) were assessed. Results indicated significantly higher serum levels of CCL11 in SCZ and BD patients compared to HC, while GDF15 levels were elevated across all psychiatric groups. A significant relationship was found between both serum cytokines and severity markers like the number of psychiatric hospitalizations. These findings suggest that increased levels of CCL11 and GDF15 may reflect systemic inflammation linked to neuroprogression and somatoprogression in these psychiatric disorders. The study emphasizes the role of inflammatory markers in understanding the comorbidities associated with these conditions and highlights the importance of integrated strategies addressing both neuropsychiatric and somatic factors to improve outcomes for patients with severe mental illnesses.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111446"},"PeriodicalIF":5.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing study reveals the potential role of the RPS26 gene in attention deficit hyperactivity disorder","authors":"Sung-Chou Li ,&nbsp;Liang-Jen Wang ,&nbsp;Ho-Chang Kuo ,&nbsp;Ching-Shu Tsai ,&nbsp;Wen-Jiun Chou ,&nbsp;Chia-Jung Li ,&nbsp;An-Chi Liu ,&nbsp;Hui-Ying Yeh ,&nbsp;Ding-Wei Chen ,&nbsp;Sheng-Yu Lee","doi":"10.1016/j.pnpbp.2025.111444","DOIUrl":"10.1016/j.pnpbp.2025.111444","url":null,"abstract":"<div><div>Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. Due to the limited availability of postmortem brain tissue, most gene expression studies in ADHD have relied on bulk RNA profiling of total white blood cells (WBCs). However, this approach obscures cell-type-specific expression patterns and limits insights into the roles of distinct leukocyte subsets in ADHD pathophysiology. Single-cell RNA sequencing (scRNA-seq) offers a solution to these challenges but has not yet been widely applied to investigate ADHD biomarkers. Emerging evidence suggests that ADHD may be associated with increased risk of cardiovascular disease, in which monocytes and macrophages are known to play key pathological roles. In this study, we aimed to explore the potential link between ADHD and cardiovascular disease by focusing on monocyte/macrophage biology.</div><div>Using scRNA-seq to analyze WBC samples from a pair of dizygotic twins discordant for ADHD, we identified 12 distinct immune cell types and discovered several differentially expressed genes, including <em>RPS26</em> in monocytes. Quantitative PCR (qPCR) validation confirmed significantly reduced <em>RPS26</em> expression in both WBCs and monocytes from individuals with ADHD. Further in vitro assays revealed that <em>RPS26</em> knockdown suppressed monocyte proliferation, potentially by promoting monocyte apoptosis. Moreover, <em>RPS26</em> knockdown impaired monocyte-to-macrophage maturation and altered the 28S to 18S RNA ratio. Collectively, these findings suggest that <em>RPS26</em> plays a regulatory role in monocyte development and differentiation, which may help explain the elevated cardiovascular risk reported in individuals with ADHD. In summary, this study highlights the functional importance of <em>RPS26</em> and provides new insights into a potential molecular link between ADHD and cardiovascular disease.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111444"},"PeriodicalIF":5.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol drinking is associated with greater calcium activity in mouse central amygdala dynorphin-expressing neurons","authors":"Christina L. Lebonville ,&nbsp;Jennifer A. Rinker ,&nbsp;Krysten O'Hara ,&nbsp;Christopher S. McMahan ,&nbsp;Michaela Hoffman ,&nbsp;Howard C. Becker ,&nbsp;Patrick J. Mulholland","doi":"10.1016/j.pnpbp.2025.111445","DOIUrl":"10.1016/j.pnpbp.2025.111445","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is a chronic disease that poses significant economic burden and health risks. It is pivotal to better understand brain mechanisms engaged by alcohol that promote misuse. The central amygdala (CeA) has emerged as a key mediator of excessive alcohol consumption in preclinical models. A dynorphin-expressing subpopulation within the CeA (CeA^Dyn) has been implicated in excessive alcohol drinking, yet how cellular activity of CeA^Dyn neurons relates to ongoing alcohol drinking is not well-understood. The current study interrogated the engagement of CeA^Dyn neurons in male and female mice during voluntary alcohol consumption using fiber photometry and compared this cellular response with that of other solutions having similar motivational and/or taste characteristics. Activity of a calcium sensor, GCaMP7f, expressed in mouse CeA^Dyn neurons was recorded and time-locked to drinking bouts. Advanced fiber photometry normalization and mixed modeling methods were developed to better resolve effects, revealing relatively large increases in CeA^Dyn neuron calcium transients after bouts of alcohol drinking compared to water or sucrose drinking. This indicates that these neurons are uniquely engaged during alcohol consumption. Alcohol-specific drinking behavior (i.e., longer bout durations) did not fully explain signal differences between alcohol and other solutions nor did the relatively increased alcohol response diminish over time. No other conditions or solutions tested reproduced the pronounced change in CeA^Dyn activity associated with alcohol drinking. These findings support the presence of a unique functional signature for alcohol in a cell population known to control excessive alcohol drinking and further advance fiber photometric normalization and analytical methods.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111445"},"PeriodicalIF":5.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The sleep-mood connection: Temperament modulates neuroinflammation, clock genes, and dopaminergic receptors expression in rats","authors":"Camila Nayane Carvalho Lima ,&nbsp;Francisco Eliclécio Rodrigues da Silva ,&nbsp;Michele Albuquerque Jales de Carvalho ,&nbsp;Jose Eduardo de Carvalho Lima ,&nbsp;Adriano José Maia Chaves-Filho ,&nbsp;Gabriel R. Fries ,&nbsp;Manoel A. Sobreira-Neto ,&nbsp;Deiziane Viana da Silva Costa ,&nbsp;Marta Maria França Fonteles ,&nbsp;Danielle S. Macêdo","doi":"10.1016/j.pnpbp.2025.111443","DOIUrl":"10.1016/j.pnpbp.2025.111443","url":null,"abstract":"<div><div>Temperament plays a critical role in individual susceptibility to mood disorders, particularly in contexts of sleep disruption, through still underexplored mechanisms. This study examined how paradoxical sleep deprivation (PSD) affects behavioral and neurobiological outcomes in high- and low-exploratory (HE and LE) Wistar rats, representing distinct temperament profiles. From a cohort of 80 periadolescent males, 20 HE and 20 LE rats were identified using an open-field test and randomly assigned to PSD or control conditions. Behavioral testing evaluated impulsivity, risk-taking, anxiety-like behavior, anhedonia, despair-like behavior, and memory performance. Biological endpoints included blood uric acid, plasma cytokines, and hippocampal oxidative stress (glutathione and lipid peroxidation), cytokines (interleukin [IL] 1β, IL-6, IL-4), gene expression of circadian regulators (<em>Clock, Bmal1, Per</em> and <em>Cry</em> genes), serotonergic and kynurenine pathway enzymes (Tryptophan Hydroxylase 2, <em>Tph2</em>; Tryptophan 2,3-Dioxygenase,<em>Tdo2</em>; Indoleamine 2,3-Dioxygenase,<em>Ido1</em>), and dopamine D1 (Drd1) and D2 receptor (Drd2) protein levels (measured by Western Blotting). PSD exacerbated risk-taking in HE rats and increased anhedonia and immobility in LE rats. Memory impairments were observed in both groups following PSD. At molecular level, HE rats exposed to PSD showed increased lipid peroxidation, inflammation, upregulation of circadian genes and <em>Tph2</em>, and elevated Drd1 expression. LE rats displayed reduced serotonergic gene expression, increased kynurenine pathway activation, and selective Drd2 upregulation. These findings indicate that temperament shapes behavioral and neurobiological vulnerability to rapid eye movement sleep loss, with distinct profiles associated with mania- and depression-like phenotypes. This supports the relevance of temperament-informed frameworks in understanding mood disorder pathophysiology and guiding personalized treatment strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111443"},"PeriodicalIF":5.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the response to Lorazepam in catatonia: a network analysis approach","authors":"Tomas Mastellari ,&nbsp;Christophe Gauld ,&nbsp;Thomas Fovet ,&nbsp;Ali Amad","doi":"10.1016/j.pnpbp.2025.111435","DOIUrl":"10.1016/j.pnpbp.2025.111435","url":null,"abstract":"<div><h3>Background</h3><div>Lorazepam, a widely used benzodiazepine, is the first-line treatment for catatonia. In case of resistance to Lorazepam, a trial-and-error approach is usually followed, increasing the risk of severe medical complications. To date, the mechanisms underlying non-response to Lorazepam remain unclear. The aims of this study were to determine whether network analysis can identify symptom-based predictors of response to Lorazepam and assess whether the structure of catatonic symptoms differs between responders and non-responders.</div></div><div><h3>Methods</h3><div>A cohort of patients with catatonia (<em>n</em> = 136) was recruited at a specialized clinical center. Network analyses were conducted using the Bush-Francis Catatonia Rating Scale items, to describe the structure of catatonic symptoms in responders and non-responders to Lorazepam. Symptom clusters were identified using a spinglass algorithm and centrality measures were compared between groups. Additionally, network outcome analyses were performed to identify clinical predictors of Lorazepam response.</div></div><div><h3>Results</h3><div>Three clusters of catatonic symptoms were identified, with similar structure between responders and non-responders. No significant differences were found in centrality measures. The most central symptoms were characteristics of hyperkinetic catatonia. Immobility / stupor emerged as the unique direct predictor of response to Lorazepam.</div></div><div><h3>Conclusion</h3><div>The overall structure of catatonic symptoms appears stable between responders and non-responders. Hypokinetic symptoms, particularly immobility and stupor, serve as strong predictors of Lorazepam response. Given the critical need for early treatment prediction to optimize therapeutic interventions and reduce catatonia-related mortality, further research is needed to refine clinical predictors of Lorazepam response.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111435"},"PeriodicalIF":5.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered reward feedback processing in methadone maintenance treatment patients: An ERP study using the monetary incentive delay task","authors":"Hua Ni ,&nbsp;Shichen Zhang ,&nbsp;Huiting Cai ,&nbsp;Guilai Zhan ,&nbsp;Zhen Lyu ,&nbsp;Liangyuan Song ,&nbsp;Taicheng Huang ,&nbsp;Zhipeng Cao ,&nbsp;Jun Chen","doi":"10.1016/j.pnpbp.2025.111440","DOIUrl":"10.1016/j.pnpbp.2025.111440","url":null,"abstract":"<div><div>Opioid use disorder (OUD) is a significant global health challenge marked by neurophysiological abnormalities affecting mood, motivation, memory, and reward processing. While methadone maintenance treatment (MMT) is widely employed to treat OUD, its impact on neural reward mechanisms remains poorly understood. In this study, we investigated the electrophysiological correlates of reward processing in 15 MMT patients and 21 healthy controls using the Monetary Incentive Delay (MID) task combined with electroencephalography (EEG). MMT patients performed the task both before and 30 min after the methadone intake. Event-related potential components, specifically feedback-related negativity (FRN) and feedback P3 (FB-P3), were compared between groups. We found that behavioral performance, including reaction times and accuracy, did not differ significantly between MMT patients and healthy controls across win and loss conditions. However, EEG results revealed that MMT patients showed significantly more negative FRN amplitudes at <strong>frontal electrodes</strong> compared to HCs under both win-hit and loss-hit conditions, suggesting their deficits in neural processing of reward feedback. No significant differences in FB-P3 amplitudes at <strong>central electrodes</strong> were observed between groups. Additionally, no significant changes in FRN amplitudes were detected in MMT patients before and after methadone administration. These findings provide preliminary evidence of altered neural processing of reward feedback in individuals receiving stable long-term MMT, and acute methadone administration did not appear to modulate these responses. Further research is needed to clarify the clinical relevance of these neural alterations and their potential role in treatment outcomes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111440"},"PeriodicalIF":5.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lateral septum activation as a central hub for reversing chronic stress-induced novelty-avoidance","authors":"Chih-Hua Chang ,&nbsp;Sheng-Feng Sung ,&nbsp;Chi-Sheng Chen ,&nbsp;Kuan-Chin Sung ,&nbsp;Hsi-Chien Wang ,&nbsp;Ya-Hsin Hsiao","doi":"10.1016/j.pnpbp.2025.111436","DOIUrl":"10.1016/j.pnpbp.2025.111436","url":null,"abstract":"<div><div>Chronic stress is a major risk for mental disorders, particularly major depression, leading to behavioral impairments such as reduced novelty-seeking behavior. This study investigates the neurobiological mechanisms underlying chronic stress-induced deficits in novelty-driven exploratory behavior. Using a chronic unpredictable stress (CUS) model in mice, we observed significant reductions in novelty-seeking behavior during Y-maze and object location tasks, accompanied by decreased dorsal hippocampal activity. Chemogenetic activation of the dorsal hippocampus restored these behaviors, highlighting its critical role in novelty-seeking. In contrast, the ventral hippocampal activation failed to reverse the deficits, emphasizing a spatially specific function of the dorsal hippocampus. Further investigation revealed that activation of the ventral tegmental area (VTA) in CUS mice increased c-Fos expression in the lateral septum (LS) and alleviated CUS-induced novelty-avoidance. Furthermore, the LS received convergent projections from the dorsal hippocampal CA1 and VTA. Selective activation of LS-projecting pathways from the dorsal hippocampus and VTA drove novelty-seeking behavior in CUS mice. These findings suggest that LS activation is a pivotal node in enhancing novelty-seeking behavior impaired by chronic stress. By integrating spatial signals from the dorsal hippocampus with motivational inputs from the VTA, the LS emerges as a promising therapeutic target for interventions aimed to counteract chronic stress-induced novelty-avoidance. This study provides comprehensive insights into the neural underpinnings of exploratory behavior under chronic stress and underscores the translational potential of targeting the LS in stress-related disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111436"},"PeriodicalIF":5.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}